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- 저자 : Isorce, N. (검색결과 1 건)
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Park, Y.K.,Park, E.S.,Kim, D.H.,Ahn, S.H.,Park, S.H.,Lee, A.R.,Park, S.,Kang, H.S.,Lee, J.H.,Kim, J.M.,Lee, S.K.,Lim, K.H.,Isorce, N.,Tong, S.,Zoulim, F.,Kim, K.H. Elsevier Science Publishers 2016 Journal of hepatology Vol. No.
<P>Background & Aims: Cytokines are key molecules implicated in the defense against virus infection. Tumor necrosis factor-alpha (TNF-alpha) is well known to block the replication of hepatitis B virus (HBV). However, the molecular mechanism and the downstream effector molecules remain largely unknown. Methods: In this study, we investigated the antiviral effect and mechanism of p22-FLIP (FLICE-inhibitory protein) by ectopic expression in vitro and in vivo. In addition, to provide the biological relevance of our study, we examined that the p22-FLIP is involved in TNF-alpha-mediated suppression of HBV in primary human hepatocytes. Results: We found that p22-FLIP, a newly discovered c-FLIP cleavage product, inhibited HBV replication at the transcriptional level in both hepatoma cells and primary human hepatocytes, and that c-FLIP conversion to p22-FLIP was stimulated by the TNF-alpha/NF-kappa B pathway. p22-FLIP inhibited HBV replication through the upregulation of HNF3 beta but downregulation of HNF4 alpha, thus inhibiting both HBV enhancer elements. Finally, p22-FLIP potently inhibited HBV DNA replication in a mouse model of HBV replication. Conclusions: Taken together, these findings suggest that the anti-apoptotic p22-FLIP serves a novel function of inhibiting HBV transcription, and mediates the antiviral effect of TNF-a against HBV replication. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</P>
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